Anatomical and functional organization of inter-areal feedback circuits in the visual cortex, and their impact on neuronal responses

 描述(申请人提供)：在过去的40年里，分层前馈模型为大多数视觉处理理论提供了基础。然而，在大脑皮层，有一个密集的反馈(FB)连接网络，将自上而下的信息从较高的处理中心发送到较低的处理中心。FB回路的解剖和功能仍然知之甚少。这是尽管FB参与了许多重要的视觉功能，如语境调节、注意力和学习。本应用的目的是了解从次级(V2)到初级视皮层(V1)的FB连接的解剖和功能组织，以及V2 FB对V1细胞反应的影响。我们将检验以下假设：1.从解剖学上讲，V2Fb由平行的通道组成，与V2的条纹间隔相关，每个通道针对特定的V1层、V1间隔和为特定的V2条纹提供输入的相同的V1细胞(目标1)。对于V1(目标2)中的视觉刺激属性的功能图，不同的通道也显示出独特的特异性。2.在功能上，V2 FB参与视觉刺激V1细胞感受野(RF)附近的周围区域引起的环绕调制(SM)(目标3)。SM是射频环境中的刺激调节V1细胞对射频内刺激的反应的能力，这一特性被认为是为自然图像的有效编码和对象边界的分割服务的(Nurminen&Angelucci，2014)参考文献43。我们对FB的解剖和功能的理解一直受到以前用于标记FB轴突和操纵其活动的方法的技术限制的阻碍。传统的示踪剂要么灵敏度低，要么标记轴突是双向的，造成了解释上的混乱 轴突标签上的。因此，关于FB连接的解剖学和功能特异性的报道相互矛盾。FB系统的失活是使用缺乏时空精确度和细胞类型选择性的方法进行的，影响到整个大脑皮层区域的细胞。这些途径不能排除FB操纵的影响是通过其他间接途径介导的。为了克服这些局限性，我们将研究FB从V2到V1的连接的解剖和功能组织，使用新的病毒介导的荧光蛋白表达来明确标记FB轴突及其突触终末。在目标1中，这些标记方法将与V1层和隔室(CO图)的染色相结合，在目标2中，将与V1功能图的光学成像相结合。在目标3中，FB神经元活动的操纵将通过视蛋白表达的FB轴突的光遗传激活来执行，同时确定这些操纵对V1细胞自发和视觉诱发的棘波活动的影响，使用线性阵列记录。这些数据将为FB功能和功能障碍的建模和假说驱动的研究提供解剖学和力学基础，并有助于更好地理解FB这一典型的皮层环路(即自上而下FB)执行的计算。

 DESCRIPTION (provided by applicant): Hierarchical feedforward models have provided a foundation for most theories of visual processing over the past 40 years. However, in the cerebral cortex there is a dense network of feedback (FB) connections sending topdown information from higher to lower processing centers. The anatomy and function of FB circuits is still poorly understood. This is despite the fact that FB has been implicated in many important visual functions such as contextual modulation, attention and learning. The goal of this application is to understand the anatomical and functional organization of FB connections from the secondary (V2) to the primary visual cortex (V1), and the impact of V2 FB on V1 cell responses. We will test the following hypotheses: 1. Anatomically, V2 FB consists of parallel channels, related to the stripe compartments of V2, with each channel targeting specific V1 layers, V1 compartments and the same V1 cells that provide input to the specific V2 stripe (Aim 1). The different channels also show unique specificities with respect to the functional maps of visual stimulus properties in V1 (Aim 2). 2. Functionally, V2 FB contributes to surround modulation (SM) caused by visual stimulation of the surround regions near the V1 cell's receptive field (RF) (Aim 3). SM is the ability of stimuli in the RF surround to modulate the responses of V1 cells to stimuli inside the RF, a property thought to serve efficient coding of natural images and segmentation of object boundaries (Nurminen & Angelucci, 2014) Ref43. Our understanding of FB anatomy and function has been hampered by the technical limitations of previous methods used to label FB axons and manipulate their activity. Conventional tracers are either poorly sensitive or label axons bidirectional, creating a confound in the interpretation of the axon label. As a result, there are conflicting reports regarding the anatomical and functional specificity of FB connections. Inactivation of FB systems has been performed using methods that lack spatiotemporal precision and cell type selectivity, affecting cells in an entire cortical area. These approaches could not rule out that the effects of FB manipulation were mediated by other indirect pathways. To overcome these limitations, we will investigate the anatomical and functional organization of FB connections from V2 to V1, using novel viral-mediated expression of fluorescent proteins to label FB axons and their synaptic terminals unambiguously. In Aim 1 these labeling methods will be combined with staining of V1 layers and compartment (CO maps), and in Aim 2 with optical imaging of V1 functional maps. In Aim 3, manipulation of FB neuron activity will be performed using optogenetic activation of opsin-expressing FB axons, while determining the effects of these manipulations on spontaneous and visually-evoked spike activity in V1 cells, recorded using linear arrays. These data will provide an anatomical and mechanistic foundation for modeling and hypothesis-driven studies of FB function and dysfunction, and lead to a better understanding of the computations performed by this canonical cortical circuit, i.e. top down FB.